AB0348 THE PROPER STUDY: A 48-WEEK ANALYSIS OF A PAN-EU REAL-WORLD STUDY OF SB5 BIOSIMILAR FOLLOWING TRANSITION FROM REFERENCE ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS, AXIAL SPONDYLOARTHRITIS OR PSORIATIC ARTHRITIS
Authors: U. Müller-Ladner, K. Gaffney, D. Jadon, M. Matucci-Cerinic, E. Chamizo Carmona, U. Freudensprung, J. Addison
Journal: Annals of the Rheumatic Diseases (2022)

Background SB5, a biosimilar to reference adalimumab (ADL), received EU marketing authorisation in 2017, based on pre-clinical and clinical phase I and III studies that demonstrated bioequivalence and comparable efficacy, safety and immunogenicity to ADL. Objectives The real-world study ‘PROPER’ is designed to provide insights into outcomes of the transition from ADL to SB5 outside the randomised, controlled, clinical trial setting. Methods Under an umbrella design, 1000 patients with immune-mediated inflammatory disease were enrolled at centres in Belgium, Germany, Ireland, Italy, Spain and the UK, and followed for 48 weeks post-transition. Eligible patients with a diagnosis of rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), ulcerative colitis or Crohn’s disease had been transitioned to SB5 as part of routine treatment following a minimum of 16 weeks’ treatment with ADL. Data were captured from patient charts retrospectively for 24 weeks prior to and prospectively and/or retrospectively up to 48 weeks after SB5 initiation. This analysis of the rheumatology cohort reports clinical characteristics, disease scores, persistence on SB5, clinical management and safety up to the closing date of November 30th, 2021. Results Of the 496 patients included in this analysis, the majority were enrolled in UK (n=174), Germany (n=145) and Spain (n=73); Italy, Ireland and Belgium enrolled 45, 44 and 15 patients respectively. At study close, 487 patients had completed 48 weeks of follow-up; 397 of those remained on SB5 throughout. Methotrexate was received as concomitant therapy by 37% of patients and 20% had received a biologic therapy prior to reference ADL. Most patients (89.3% of RA, 92.1% of axSpA, 97.3% of PsA) transitioned to SB5 at the same dose regimen received for ADL. Clinical characteristics, SB5 dose and flare are detailed in Table 1, disease scores in Figure 1. Table 1. Patient clinical characteristics, SB5 dose, flare RA (N=207) axSpA (N=127) PsA (N=162) Age at SB5 initiation (years), mean (SD); IQR 60.1 (11.8) 53.0, 68.0 50.3 (13.4) 38.0, 61.0 53.3 (12.0) 45.0, 62.0 Duration of disease (years), mean (SD); IQR 13.3 (11.4) 5.0, 19.5 18.8 (13.5) 9.0, 25.0 12.2 (9.9) 4.0, 19.0 n % n % n % Women 150 72.5 40 31.5 73 45.1 Patients receiving SB5 40mg Q2W Baseline 152 73.4 115 90.6 149 92.0 Week 48 132 72.5 93 87.7 124 91.9 Episodes of Flare 0 187 90.3 107 84.3 139 85.8 1 20 9.7 18 14.2 20 12.3 2 0 0.0 2 1.6 3 1.9 How was Flare diagnosed Disease score 11 55.0 7 31.8 10 38.5 Patient-reported symptoms 19 95.0 22 100.0 26 100.0 Secondary Loss of Response 3 15.0 0 0.0 7 26.9 Action taken for Flare Biologic therapy dose adjusted 4 20.0 2 9.1 5 19.2 Non-biologic therapy dose adjusted 8 40.0 3 13.6 9 34.6 Clinical investigation 0 0.0 1 4.5 3 11.5 Other* 9 45.0 13 59.1 16 61.5 *Includes cessation of therapy, prescription of corticosteroids, physical exercise, no action. IQR, interquartile range; SD, standard deviation; Q2W once two-weekly. Figure 1. Disease scores (paired patients), mean (95% CI) Fifteen patients each experienced one unrelated Serious Adverse Event (SAE): 2 in the axSpA cohort [tachycardia, intracranial haemorrhage]; 6 in the PsA cohort [myocardial infarct (2), breast carcinoma, COVID-19, gallbladder calculus, dyspnoea]; 7 in the RA cohort [facial numbness, depression, COVID-19, pneumonia, diverticulitis, parvovirus, coronary occlusion]. Two patients reported SAEs considered causally related to SB5: Herpes zoster and pneumonia (RA cohort), and ALS with worsening (PsA cohort). Conclusion This analysis of a large, contemporary cohort of EU patients with established RA, axSpA or PsA shows treatment effectiveness maintained at 48 weeks after switching from ADL to SB5, with most patients continuing on SB5 Q2W throughout. Episodes of flare were uncommon, and the importance of patient-reported symptoms in recognition of flare is evident. No new safety signals were observed. Acknowledgements Statistical services were provided by FGK Clinical Research GmbH, Munich, Germany. Data management services were provided by Worldwide Clinical trial, Research Triangle Park, NC, USA. Funding was provided by Biogen International GmbH. Disclosure of Interests Ulf Müller-Ladner Consultant of: Biogen, Grant/research support from: Biogen, Karl Gaffney Speakers bureau: Novartis, UCB, AbbVie, Lilly, Consultant of: Novartis, UCB, AbbVie, Lilly, Pfizer, Grant/research support from: NAAS, AbbVie, Pfizer, UCB, Novartis, Lilly, Cellgene, Celltrion, Janssen, Gilead, Biogen, Deepak Jadon Consultant of: AbbVie, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Oxford University Press, Pfizer, Roche, Sandoz, UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Oxford University Press, Pfizer, Roche, Sandoz, UCB, Marco Matucci-Cerinic Consultant of: Chemomab, Biogen, Pfizer, Lilly, Behring, Janssen, MSD, Eugenio Chamizo Carmona Speakers bureau: Abbvie, Amgen, Biogen, BMS, Celgene, Eli Lilly, Fresenius-Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: Abbvie, Amgen, Biogen, BMS, Celgene, Eli Lilly, Fresenius-Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, and UCB, Ulrich Freudensprung Shareholder of: May hold stock in Biogen, Employee of: Biogen, Janet Addison Shareholder of: May hold stock in Biogen, Employee of: Biogen